IL-23 is a cytokine believed to be important for activation of a range of inflammatory cells that are required for the induction of chronic inflammation. IL-23 has a separate but complementary function to IL-12, a heterodimeric cytokine of 70 KDa consisting of covalently linked p40 and p35 subunits. IL-23 is composed of the same p40 subunit as IL-12 but covalently paired with a p19 subunit (Langrish et. al., Immunological Reviews 202:96-105, 2004).
Furthermore, IL-23 has been implicated to play an important role in memory/pathogenic T-cell responses by promoting the secretion of the pro-inflammatory cytokine IL-17 from activated T cells. There is increasing evidence that high levels of IL-17 are associated with autoimmune, inflammatory diseases including rheumatoid arthritis, psoriasis, and multiple sclerosis (Aggarwal et al., J. Biol. Chem 278(3):1910-1914, 2003). Thus, a neutralizing antibody to IL-23 will inhibit the secretion and pro-inflammatory effects of IL-17 and ultimately, the effect of IL-17 on inflammatory diseases.
Although antibodies to human IL-23 have been reported previously, high affinity, neutralizing antibodies to human IL-23 recognizing a specific epitope on the p19 subunit, have not been disclosed. Without question, there is a need for disease modifying therapies for the treatment of autoimmune disease.
Accordingly, there is a need for a high affinity neutralizing antibody that specifically binds the p19 subunit of IL-23 and thereby blocks the pro-inflammatory actions of IL-17, which can be utilized as a therapeutic agent. A high affinity antibody that specifically binds the p19 subunit of IL-23 is also desirable in that it may allow the antibody to be administered to a patient subcutaneously rather than intravenously. There is also a need for an antibody that specifically binds the p19 subunit of L-23 with a low IC50 value in an IL-23 inhibition assay in order to generate a therapeutic anti-IL-23 antibody with a minimum effective therapeutic dose. The present invention satisfies these needs and provides related advantages, therefore providing a useful treatment of autoimmune disease.